RIPK1 ubiquitination: Evidence, correlations and the undefined

Abstract

Over the last two decades the mechanisms that underpin cell survival and cell death have been intensively studied. One molecule in particular, Receptor Interacting Protein Kinase 1 (RIPK1), has gained interest due to the ability to function upstream of both NF-κB signaling and caspase-dependent and -independent cell death. RIPK1 is critical in determining cell fate downstream of cytokine signaling receptors such as the Tumour Necrosis Factor Receptor Super Family (TNFRSF) and the innate immune Toll-like receptors. Various studies have attempted to untangle how ubiquitination of RIPK1 dictates signaling outcomes; however, due to the complex nature of ubiquitin signaling it has been difficult to prove that ubiquitination of RIPK1 does in fact influence signaling outcomes. Therefore, we ask the question: What do we really know about RIPK1 ubiquitination, and, to what extent can we conclude that ubiquitination of RIPK1 impacts RIPK1-mediated signaling events?

Keywords: RIPK1; Ubiquitination.